The objective of this study is to use microarray analysis to more thoroughly understand the host response to tuberculosis in infected guinea pigs, widely regarded as the most relevant small animal model of this disease. Using bioinformatics, we propose to further probe the nature of the global immune response in this animal model, both to clinically relevant [high/low transmission] W-Beijing strains of M.tuberculosis, and in animals previously vaccinated. We are specifically interested in further examining the possibility that new vaccines will be ineffective due to the induction in the host of regulatory T cell networks that respond to the highly virulent W-Beijing strains. Over the past year our two collaborative sites have worked together closely to solve a variety of technical problems regarding isolation of guinea pig lung RNA, as well as transport issues, and we now have a workable protocol to base these studies on [and as a consequence, some preliminary data]. The plan is to vaccinate and challenge guinea pigs in the state of the art biosafety level-III facilities at CSU, then send isolated RNA to Genotypic in Bangalore for further analysis by microarray. While this technology is no longer """"""""new"""""""" this will be the first time it has been done in the guinea pig model, and the first time in the specific context of vaccination and tuberculosis [thus making it highly responsive to the US-Indo Vaccine Action Program initiative]. As a result, it has high potential to provide new information about the host response in this important and relevant animal model.

Public Health Relevance

India is a focal point for the current tuberculosis pandemic. There is still much to be learned about the host response to tuberculosis and how this influences whether new vaccines might work or not. This proposal represents a collaboration between a group at CSU who are experts in animal models of tuberculosis, including the effects of vaccination, and a group in India specializing in bioinformatics.